scholarly journals Insulin-response epigenetic activation of Egr-1 and JunB genes at the nuclear periphery by A-type lamin-associated pY19-Caveolin-2 in the inner nuclear membrane

2015 ◽  
Vol 43 (6) ◽  
pp. 3114-3127 ◽  
Author(s):  
Kyuho Jeong ◽  
Hayeong Kwon ◽  
Jaewoong Lee ◽  
Donghwan Jang ◽  
Yunbae Pak
Keyword(s):  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Insulin Response ◽  
Inner Nuclear Membrane

scholarly journals Targeting of the SUN protein Mps3 to the inner nuclear membrane by the histone variant H2A.Z

2011 ◽  
Vol 193 (3) ◽  
pp. 489-507 ◽  
Author(s):  
Jennifer M. Gardner ◽  
Christine J. Smoyer ◽  
Elizabeth S. Stensrud ◽  
Richard Alexander ◽  
Madelaine Gogol ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Three Dimensional ◽  
Nuclear Architecture ◽  
Histone Variant ◽  
Inner Nuclear Membrane ◽  
Histone Fold ◽  
Acidic Domain ◽  
Histone Fold Domain ◽  
The Relationship

Understanding the relationship between chromatin and proteins at the nuclear periphery, such as the conserved SUN family of inner nuclear membrane (INM) proteins, is necessary to elucidate how three-dimensional nuclear architecture is established and maintained. We found that the budding yeast SUN protein Mps3 directly binds to the histone variant H2A.Z but not other histones. Biochemical and genetic data indicate that the interaction between Mps3 and H2A.Z requires the Mps3 N-terminal acidic domain and unique sequences in the H2A.Z N terminus and histone-fold domain. Analysis of binding-defective mutants showed that the Mps3–H2A.Z interaction is not essential for any previously described role for either protein in nuclear organization, and multiple lines of evidence suggest that Mps3–H2A.Z binding occurs independently of H2A.Z incorporation into chromatin. We demonstrate that H2A.Z is required to target a soluble Mps3 fragment to the nucleus and to localize full-length Mps3 in the INM, indicating that H2A.Z has a novel chromatin-independent function in INM targeting of SUN proteins.

scholarly journals The inner nuclear membrane proteins Man1 and Ima1 link to two different types of chromatin at the nuclear periphery inS. pombe

Nucleus ◽  
2012 ◽  
Vol 3 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Babett Steglich ◽  
Guillaume Filion ◽  
Bas van Steensel ◽  
Karl Ekwall
Keyword(s):  
Membrane Proteins ◽  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Inner Nuclear Membrane ◽  
Different Types

scholarly journals Cytomegalovirus Primary Envelopment Occurs at Large Infoldings of the Inner Nuclear Membrane

2006 ◽  
Vol 81 (6) ◽  
pp. 3042-3048 ◽  
Author(s):  
Christopher Buser ◽  
Paul Walther ◽  
Thomas Mertens ◽  
Detlef Michel
Keyword(s):  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Freeze Substitution ◽  
Murine Cytomegalovirus ◽  
Membrane Domain ◽  
Structural Element ◽  
Membrane Area ◽  
Inner Nuclear Membrane ◽  
Transmission Electron ◽  
Plastic Embedding

ABSTRACT We have investigated the morphogenesis of human and murine cytomegalovirus by transmission electron microscopy after high-pressure freezing, freeze substitution, and plastic embedding. We observed large tubular infoldings of the inner nuclear membrane that were free of lamina and active in primary envelopment and subsequent transport of capsids to the nuclear periphery. Semiquantitative determinations of the enlarged inner nuclear membrane area and the location of the primary envelopment of nucleocapsids demonstrated that this structure represents a virus-induced specialized membrane domain at which the particles are preferentially enveloped. This is a previously undescribed structural element relevant in cytomegalovirus morphogenesis.

scholarly journals The HSV1 Tail-Anchored Membrane Protein pUL34 Contains a Basic Motif That Supports Active Transport to the Inner Nuclear Membrane Prior to Formation of the Nuclear Egress Complex

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1544
Author(s):  
Christina Funk ◽  
Débora Marques da Silveira e Santos ◽  
Melanie Ott ◽  
Verena Raschbichler ◽  
Susanne M. Bailer
Keyword(s):  
Nuclear Membrane ◽  
Insertion Site ◽  
Nuclear Periphery ◽  
Pore Channel ◽  
Inner Nuclear Membrane ◽  
Nuclear Egress ◽  
Viral Mutant ◽  
Membrane Budding ◽  
Simplex Virus ◽  
Host Nucleus

Herpes simplex virus type 1 nucleocapsids are released from the host nucleus by a budding process through the nuclear envelope called nuclear egress. Two viral proteins, the integral membrane proteins pUL34 and pUL31, form the nuclear egress complex at the inner nuclear membrane, which is critical for this process. The nuclear import of both proteins ensues separately from each other: pUL31 is actively imported through the central pore channel, while pUL34 is transported along the peripheral pore membrane. With this study, we identified a functional bipartite NLS between residues 178 and 194 of pUL34. pUL34 lacking its NLS is mislocalized to the TGN but retargeted to the ER upon insertion of the authentic NLS or a mimic NLS, independent of the insertion site. If co-expressed with pUL31, either of the pUL34-NLS variants is efficiently, although not completely, targeted to the nuclear rim where co-localization with pUL31 and membrane budding seem to occur, comparable to the wild-type. The viral mutant HSV1(17+)Lox-UL34-NLS mt is modestly attenuated but viable and associated with localization of pUL34-NLS mt to both the nuclear periphery and cytoplasm. We propose that targeting of pUL34 to the INM is facilitated by, but not dependent on, the presence of an NLS, thereby supporting NEC formation and viral replication.

scholarly journals Lamin-dependent Localization of UNC-84, A Protein Required for Nuclear Migration in Caenorhabditis elegans

2002 ◽  
Vol 13 (3) ◽  
pp. 892-901 ◽  
Author(s):  
Kenneth K. Lee ◽  
Daniel Starr ◽  
Merav Cohen ◽  
Jun Liu ◽  
Min Han ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Membrane Proteins ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Nuclear Migration ◽  
Cell Stage ◽  
Inner Nuclear Membrane ◽  
Late Anaphase

Mutations in the Caenorhabditis elegans unc-84 gene cause defects in nuclear migration and anchoring. We show that endogenous UNC-84 protein colocalizes with Ce-lamin at the nuclear envelope and that the envelope localization of UNC-84 requires Ce-lamin. We also show that during mitosis, UNC-84 remains at the nuclear periphery until late anaphase, similar to known inner nuclear membrane proteins. UNC-84 protein is first detected at the 26-cell stage and thereafter is present in most cells during development and in adults. UNC-84 is properly expressed in unc-83 andanc-1 lines, which have phenotypes similar tounc-84, suggesting that neither the expression nor nuclear envelope localization of UNC-84 depends on UNC-83 or ANC-1 proteins. The envelope localization of Ce-lamin, Ce-emerin, Ce-MAN1, and nucleoporins are unaffected by the loss of UNC-84. UNC-84 is not required for centrosome attachment to the nucleus because centrosomes are localized normally in unc-84 hyp7 cells despite a nuclear migration defect. Models for UNC-84 localization are discussed.

scholarly journals A Role for Nuclear F-Actin Induction in Human Cytomegalovirus Nuclear Egress

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Adrian R. Wilkie ◽  
Jessica L. Lawler ◽  
Donald M. Coen
Keyword(s):  
Human Cytomegalovirus ◽  
Nuclear Membrane ◽  
Actin Filaments ◽  
Human Fibroblasts ◽  
Nuclear Periphery ◽  
Viral Gene Expression ◽  
Actin Binding ◽  
Viral Gene ◽  
Inner Nuclear Membrane ◽  
Nuclear Egress

ABSTRACTHerpesviruses, which include important pathogens, remodel the host cell nucleus to facilitate infection. This remodeling includes the formation of structures called replication compartments (RCs) in which herpesviruses replicate their DNA. During infection with the betaherpesvirus, human cytomegalovirus (HCMV), viral DNA synthesis occurs at the periphery of RCs within the nuclear interior, after which assembled capsids must reach the inner nuclear membrane (INM) for translocation to the cytoplasm (nuclear egress). The processes that facilitate movement of HCMV capsids to the INM during nuclear egress are unknown. Although an actin-based mechanism of alphaherpesvirus capsid trafficking to the INM has been proposed, it is controversial. Here, using a fluorescently-tagged, nucleus-localized actin-binding peptide, we show that HCMV, but not herpes simplex virus 1, strongly induced nuclear actin filaments (F-actin) in human fibroblasts. Based on studies using UV inactivation and inhibitors, this induction depended on viral gene expression. Interestingly, by 24 h postinfection, nuclear F-actin formed thicker structures that appeared by super-resolution microscopy to be bundles of filaments. Later in infection, nuclear F-actin primarily localized along the RC periphery and between the RC periphery and the nuclear rim. Importantly, a drug that depolymerized nuclear F-actin caused defects in production of infectious virus, capsid accumulation in the cytoplasm, and capsid localization near the nuclear rim, without decreasing capsid accumulation in the nucleus. Thus, our results suggest that for at least one herpesvirus, nuclear F-actin promotes capsid movement to the nuclear periphery and nuclear egress. We discuss our results in terms of competing models for these processes.IMPORTANCEThe mechanisms underlying herpesvirus nuclear egress have not been fully determined. In particular, how newly assembled capsids move to the inner nuclear membrane for envelopment is uncertain and controversial. In this study, we show that HCMV, an important human pathogen, induces actin filaments in the nuclei of infected cells and that an inhibitor of nuclear F-actin impairs nuclear egress and capsid localization toward the nuclear periphery. Herpesviruses are widespread pathogens that cause or contribute to an array of human diseases. A better understanding of how herpesvirus capsids traffic in the nucleus may uncover novel targets for antiviral intervention and elucidate aspects of the nuclear cytoskeleton, about which little is known.

scholarly journals Evolvement of LEM proteins as chromatin tethers at the nuclear periphery

2011 ◽  
Vol 39 (6) ◽  
pp. 1735-1741 ◽  
Author(s):  
Andreas Brachner ◽  
Roland Foisner
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Nuclear Periphery ◽  
Transmembrane Proteins ◽  
Signal Transducer ◽  
Protein Inhibitor ◽  
Inner Nuclear Membrane ◽  
Unicellular Eukaryotes ◽  
Attachment Factor ◽  
Affect Gene Expression

The nuclear envelope in eukaryotic cells has important roles in chromatin organization. The inner nuclear membrane contains over 60 transmembrane proteins. LEM [LAP2 (lamina-associated polypeptide 2)/emerin/MAN1] domain-containing proteins of the inner nuclear membrane are involved in tethering chromatin to the nuclear envelope and affect gene expression. They contain a common structural, bihelical motif, the so-called LEM domain, which mediates binding to a conserved chromatin protein, BAF (barrier to autointegration factor). Interestingly, this domain is highly related to other bihelical motifs, termed HeH (helix–extension–helix) and SAP {SAF (scaffold attachment factor)/acinus/PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)]} motifs, which are directly linked to DNA. In the present paper, we summarize evidence that the LEM motif evolved from the HeH and SAP domains concomitantly with BAF. In addition, we discuss the potential evolution of HeH/SAP and LEM domain-containing proteins and their role in chromatin tethering and gene regulation from unicellular eukaryotes to mammals.

Lamin B receptor: role on chromatin structure, cellular senescence and possibly aging

2020 ◽  
Vol 477 (14) ◽  
pp. 2715-2720
Author(s):  
Susana Castro-Obregón
Keyword(s):  
Cellular Senescence ◽  
Nuclear Membrane ◽  
Chromatin Structure ◽  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Chimeric Protein ◽  
Nuclear Lamina ◽  
Lamin B ◽  
Inner Nuclear Membrane ◽  
Lamin B Receptor

The nuclear envelope is composed by an outer nuclear membrane and an inner nuclear membrane, which is underlain by the nuclear lamina that provides the nucleus with mechanical strength for maintaining structure and regulates chromatin organization for modulating gene expression and silencing. A layer of heterochromatin is beneath the nuclear lamina, attached by inner nuclear membrane integral proteins such as Lamin B receptor (LBR). LBR is a chimeric protein, having also a sterol reductase activity with which it contributes to cholesterol synthesis. Lukasova et al. showed that when DNA is damaged by ɣ-radiation in cancer cells, LBR is lost causing chromatin structure changes and promoting cellular senescence. Cellular senescence is characterized by terminal cell cycle arrest and the expression and secretion of various growth factors, cytokines, metalloproteinases, etc., collectively known as senescence-associated secretory phenotype (SASP) that cause chronic inflammation and tumor progression when they persist in the tissue. Therefore, it is fundamental to understand the molecular basis for senescence establishment, maintenance and the regulation of SASP. The work of Lukasova et al. contributed to our understanding of cellular senescence establishment and provided the basis that lead to the further discovery that chromatin changes caused by LBR reduction induce an up-regulated expression of SASP factors. LBR dysfunction has relevance in several diseases and possibly in physiological aging. The potential bifunctional role of LBR on cellular senescence establishment, namely its role in chromatin structure together with its enzymatic activity contributing to cholesterol synthesis, provide a new target to develop potential anti-aging therapies.

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